Age-related macular degeneration (AMD) is the leading cause of legal blindness among people over 65. In industrial countries at least one third of persons over 75 have clinical signs of the disease (21). There are two distinct forms of AMD, known as “wet AMD” and “dry AMD”. The characteristics of each are described hereinbelow. The only current treatment for dry AMD is dietary antioxidant and mineral supplements. Although there are several current therapies for the more advanced wet form, the only current treatment for dry AMD is daily oral administration of a mixture of antioxidants, vitamins, and metals. This delays progression of dry AMD and slows conversion of dry to wet AMD in about 25% of patients (1, 2, 3). Age-related macular degeneration most often presents first as the dry form that advances to the wet form in 10-15% of the patients. More serious vision loss is associated with the wet form, but up to 20% of legal blindness is due to the dry form.
The dry form of AMD is characterized by macular drusen which are pigmented areas containing dead cells and metabolic products that distort the retina and eventually cause loss of acute vision (4). The wet form is characterized by new blood vessel growth into the retina and subsequent leakage causing catastrophic damage and resulting in severe vision loss.
The retina is a highly metabolizing tissue and requires a high choroidal blood flow to provide oxygen and remove metabolites and dead cells. The necessary blood circulates in the capillaries of the choroid layer of the eye between the retina and sclera and supplies oxygen and nutrients to the reticular pigment epithelium (RPE) and the photoreceptors of the retina. On a weight basis the retina is the most oxygen utilizing tissue in the body with a relative oxygen consumption 50% greater than the brain or kidneys (32). Most of the oxygen is used in the photoreceptors, and thus the RPE and the retina are subjected to the brutal combination of ‘toxic oxygen’ and UV radiation. One function of the RPE is to each day degrade and dispose of 10% of the outer segments of the photoreceptors. The metabolic products and non-recycled degradation products are removed by transfer to blood in the choroidal capillaries.
Drusen, which are the tiny yellow or white accumulations of extracellular material that build up in Bruch's membrane of the eye, are normal with advancing age, and most people over 40 have some hard drusen. However, the presence of larger and more numerous drusen in the macula is a common early sign of AMD and are indicators of increased risk of the complications of AMD. Drusen in the area of the macula interfere with vision by interfering with the light path thus preventing sharp focus on the macular portion of the retina necessary to obtain good visual acuity. An important factor in the formation of drusen is poor blood circulation in the choroid due to constriction and hardening of the capillaries. This allows dead cells and toxic metabolites to accumulate.
The landmark study by the AREDS group found that subjects at high risk for developing advanced stages of AMD reduced this risk by about 25% when treated with a combination of antioxidants (vitamin C, Vitamin E, and beta-carotene/Vitamin A) and minerals (zinc and copper) (3). It also found that the use of this dietary supplement also reduced the risk of central vision loss by 19%. The trial included 3640 participants who had at least early stage AMD. The use of beta-carotene by smokers, or even former smokers, led to an increased risk of cancer. New formulations have been developed in which the beta-carotene has been replaced by a mixture of lutein and zeaxanthin, or lutein alone. These are carotinoids similar to beta-carotene, and are also potent anti-oxidants (28, 29).